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CN108084192A - A kind of method that micro passage reaction carries out cyan-hydrolysis reaction - Google Patents

A kind of method that micro passage reaction carries out cyan-hydrolysis reaction Download PDF

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Publication number
CN108084192A
CN108084192A CN201711463244.3A CN201711463244A CN108084192A CN 108084192 A CN108084192 A CN 108084192A CN 201711463244 A CN201711463244 A CN 201711463244A CN 108084192 A CN108084192 A CN 108084192A
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reaction
micro
hydrolysis
method described
compound
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CN108084192B (en
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曾伟
滕坤
于淼
赫玲爽
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Dalian Microchem Co Ltd
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Dalian Microchem Co Ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30Micromixers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0053Details of the reactor
    • B01J19/0073Sealings
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0093Microreactors, e.g. miniaturised or microfabricated reactors
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/24Stationary reactors without moving elements inside
    • B01J19/2415Tubular reactors
    • B01J19/2425Tubular reactors in parallel
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00Formation or introduction of functional groups containing oxygen
    • C07B41/08Formation or introduction of functional groups containing oxygen of carboxyl groups or salts, halides or anhydrides thereof
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/26Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing carboxyl groups by reaction with HCN, or a salt thereof, and amines, or from aminonitriles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/02Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
    • C07C319/12Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols by reactions not involving the formation of mercapto groups
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/08Preparation of carboxylic acids or their salts, halides or anhydrides from nitriles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00049Controlling or regulating processes
    • B01J2219/00051Controlling the temperature
    • B01J2219/00054Controlling or regulating the heat exchange system
    • B01J2219/00056Controlling or regulating the heat exchange system involving measured parameters
    • B01J2219/00058Temperature measurement
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00049Controlling or regulating processes
    • B01J2219/00051Controlling the temperature
    • B01J2219/00074Controlling the temperature by indirect heating or cooling employing heat exchange fluids
    • B01J2219/00087Controlling the temperature by indirect heating or cooling employing heat exchange fluids with heat exchange elements outside the reactor

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

The invention discloses a kind of methods that the reaction of cyano class compound hydrolysis is carried out based on micro passage reaction, the compound containing cyano group carries out cyan-hydrolysis class reaction under the action of alkalescence or acid and alkali substance using micro passage reaction specifically in molecule.In present invention process the uniform mixing of raw material moment and efficient heat transfer are realized using micro passage reaction;When solving most important cyano class compound and being hydrolyzed using alkali, slug present in production process is dangerous;The equivalent proportion of material in reaction process is also reduced simultaneously;Reduce side reaction;And dozens of minutes will be foreshortened to the reaction time even tens seconds.In a word, present invention process improves the security of operation, realizes the safety amplification production of cyano class compound, and shortens the reaction time of cyano class compound hydrolysis, improve the selectivity and reaction efficiency of reaction, reduce the energy consumption in production, improve the utilization rate of raw material, make production process more environmentally friendly, low production cost, meanwhile use that occupation area of equipment is small, production capacity is high, greatly improve production efficiency and ability.

Description

A kind of method that micro passage reaction carries out cyan-hydrolysis reaction
Technical field
The present invention relates to a kind of method that micro passage reaction carries out cyan-hydrolysis reaction, specifically in microchannel plate It answers in device and reaction is hydrolyzed containing cyano group and lye or acid solution in molecule, generate the compound containing carboxyl, belong to Organic synthesis field.
Background technology
Micro-reacting tcchnology originates from the last century 90's, and the advantage of microreactor gradually highlights in recent years, and recognizes Microreactor is better than conventional mass-and heat-transfer ability, and microreactor then is applied to the field of chemical synthesis;Microreactor develops To today, oneself changes liquid flow pattern by reaction channel and forms infinitesimal ruler through no longer pursuing the small of reaction channel merely The liquid stream of degree forms efficiently quick mass-and heat-transfer.Using these advantages, can be very good to solve to ask present in popular response Topic.
Such as cyan-hydrolysis reaction in popular response, carried out under conditions of acid or alkalescence, cyano class compound water first Solution generation amide, the reaction was continued ultimately produces carboxylic acid or carboxylate.Cyano class compound is all in pesticide, dyestuff and medical domain A kind of important organic synthesis intermediate can not only hydrolyze preparation acid, can also be reduced into amine, be prepared as aminopropionitrile hydrolyzes Beta-alanine, it is more extensive in the application of chemical industry synthesis field, and with important application value.This kind of reaction normal conditions are in alkali Property under the conditions of hydrolysis can be relatively complete, and cannot react thorough under acid condition, under normal temperature and pressure conditions cyan-hydrolysis when Between it is longer, hydrolysis efficiency is low, and often reaction cannot be carried out thoroughly, and obtained the mixture of amide and carboxylic acid, made what is finally obtained Product purity is inadequate, therefore just needs to improve the temperature and acid-base value of hydrolysis, especially under common alkaline condition, improves temperature The violent aerogenesis of meeting, it is difficult to control reaction, risk is bigger;And it is carried out not exclusively under popular response acid condition, it is necessary to increase Acid amount, these excessive soda acids also need to be neutralized, and cause unnecessary waste and environmental pollution.
The content of the invention
Present invention is generally directed to it is above-mentioned it is conventional carry out cyan-hydrolysis reaction when can there are the problem of, it is proposed that one kind is more pacified Entirely, economic, environmental protection hydrolysis preparation process.We utilize the quick mixed material of micro passage reaction, quick separating, efficiently The characteristic of mass-and heat-transfer carry out such hydrolysis and achieve more excellent effect;Improve the conversion ratio of reaction, while by It is rapidly separated in reacting rear material, reduces the generation of side reaction, and reaction end can be controlled well;Even more important It is, using microreactor, to avoid in popular response using the danger of alkali high temperature and high pressure hydrolysis reaction slug, decrease use The equivalents that acid is hydrolyzed, this has been considerably improved industrial security and feasibility;Meanwhile closed reaction system Also safety guarantee is provided for operating personnel.
The present invention has carried out a series of cyano compound in acidity in micro passage reaction in order to achieve the above object Or the reaction being hydrolyzed under alkaline condition.More importantly lab scale and zero amplification of amplification production can be realized using microreactor Effect, thus such hydrolysis present invention studied after can be amplified production without involving an inventive effort.This hair The bright technical solution used for:
A kind of method that micro passage reaction carries out cyan-hydrolysis reaction contains the change of cyano group (- C ≡ N) in molecule It closes object in a solvent, adds in alkalescence or acidic materials, using microreactor system under the conditions of 0-150 DEG C, 0.1-10Mpa, into The reaction of row hydrolysis.
Further, the compound containing cyano group (- C ≡ N) is aliphatic compound in the molecule.Preferably Straight chain or annular at least containing there are one the aliphatic compounds of cyano containing 3-14 carbon atom;
Further, the cyano group of reaction can be hydrolyzed there are one at least containing in compound structure.
Further, alkaline matter in sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate or other alkali at least It is a kind of.Basic hydrolysis can avoid violent aerogenesis to avoid reaction slug.
Further, acidic materials are at least one of sulfuric acid, hydrochloric acid, phosphoric acid or other acid.With popular response phase Compare, the usage amount of acid can be greatly reduced.
Further, solvent is water, alcohols, glacial acetic acid or other organic solvents.
Further, the molar ratio of the compound containing cyano group (- C ≡ N) and alkalescence or acidic materials is in molecule 1:1-6, wherein preferably 1:1-1.05.
Further, preferred 80-120 DEG C of reaction temperature.
Further, hydrolysis time 0.1s-60min, wherein it is preferred that time 1-15min.
Further, the preferred pressure of reaction pressure is 1-5MPa.
Further, the micro channel reactor system includes the constant flow pump being sequentially communicated, micro-mixer, tubulation reaction Device, heat exchanger, it is described to be placed in constant temperature bath.
Further, micro channel reactor system includes:Raw material storage tank 2, feed pump 2, micro-mixer 1 (can appoint Selected from CPMM series, SIMM series, Starlam series), shell-and-tube reactor 1 (preferably stainless steel), 3, heat exchanger, temperature Degree probe 5, temperature indicator 1, counterbalance valve 1, receiving tank 1;
The operating process of cyan-hydrolysis reaction is preferably carried out using micro passage reaction:
1) microreactor system is attached;
2) by micro passage reaction by counterbalance valve back pressure, pressure is reached in micro channel reactor system;
3) micro-mixer U and shell-and-tube reactor, heat exchanger are warming up to reaction temperature by constant temperature bath;
4) system balancing and calibration;
5) raw material and catalyst are fed through feed pump, are mixed in micro-mixer, through shell-and-tube reactor, heat exchanger certain At a temperature of, condensation reaction is completed in certain time;
6) material that reaction is completed enters receiving tank storage at lower temperature, waits to post-process;
7) termination of pumping, cleaning system send material to vapor detection.
It compares with the prior art, the present invention has following advantageous effect:
Micro passage reaction is closed system, can avoid contact with harmful substance;The present invention can realize the quick of material Contact, then moment chemically react, will shorten in the reaction time thousands of times;It can be very good to carry out mass-and heat-transfer, avoid Using the danger of alkali high temperature and high pressure hydrolysis reaction slug in popular response, industrial security and feasibility are improved;Subtract Lack the equivalents that cyan-hydrolysis is carried out using acid or alkaline matter, avoided and excessive soda acid is adjusted after having reacted, reduce life Produce cost, safety and environmental protection;The reaction time is accurately controlled, quick separating can be quenched, avoided from system after the completion of reaction Side reaction occurs, and improves percent hydrolysis.
In present invention process the uniform mixing of raw material moment and efficient heat transfer are realized using micro passage reaction;It solves most When main cyano class compound is hydrolyzed using alkali, slug present in production process is dangerous;Also reduce reaction simultaneously The equivalent proportion of material in the process;Reduce side reaction;And dozens of minutes will be foreshortened to the reaction time even tens seconds.Always It, present invention process improves the security of operation, realizes the safety amplification production of cyano class compound, and shortens The reaction time of cyano class compound hydrolysis improves the selectivity and reaction efficiency of reaction, and the energy reduced in production disappears Consumption, improves the utilization rate of raw material, makes production process more environmentally friendly, low production cost, meanwhile, use occupation area of equipment It is small, production capacity is high, greatly improve production efficiency and ability.
Description of the drawings
Fig. 1 is present invention process flow chart
Sequence number Letter Explanation Sequence number Letter Explanation
1 P=XX Pump 7 TI-XX Thermometer
2 V-XX Charging/receiving tank 8 BPV-XX Counterbalance valve
3 F-XX Filter 9 PG-XX Pressure gauge
4 PT-XX Pressure transmitter 10 CV-XX Check valve
5 R-XX Reactor 11 HEX-XX Heat exchanger
6 T-XX Rectifying column
Raw material storage tank V-01, V-02;Product pans V-03;Feed pump P-01, P-02;Micro- heat exchanger HEX-01, HEX- 02、HEX-03;Micro-mixer MI-01;Stainless steel shell-and-tube reactor R-01;Counterbalance valve BVP-01;Temp probe TI-01, TI- 02、TI-03、TI-04、TI-05。
Raw material storage tank v-01 connection feed pumps p-01 enters heat exchanger HEX-01 (for heating raw material), raw material storage tank v- 02 connection feed pump p-02 enters heat exchanger HEX-02 (for heating raw material), the reaction solution come out from HEX-01 and HEX-02 Into micro-mixer MI-01, shell-and-tube reactor R-01 is then flowed sequentially through, heat exchanger HEX-03 (is used to cool down to reaction solution), Eventually enter into receiving tank V-03.
Specific embodiment
Following non-limiting examples can make those of ordinary skill in the art be more fully understood the present invention, but not with Any mode limits the present invention.Reagent and material described in following embodiments, unless otherwise specified, are commercially obtained , the present invention can carry out cyan-hydrolysis this one kind reaction, and such reaction is not limited only to described in embodiment with alkali or acid, after Processing method is also not limited to described in the embodiment of the present invention, specifically gives representational embodiment.
As shown in Figure 1, micro channel reactor system includes raw material storage tank 2, feed pump 2, micro-mixer 1 (can appoint Selected from CPMM series, SIMM series, Starlam series), stainless steel shell-and-tube reactor 1,3, heat exchanger, temp probe 5, Temperature indicator 1, counterbalance valve 1, receiving tank 1.
Temp probe TI-01 is used to test the temperature of HEX-01 outlets liquid;Temp probe TI-02 is used to test HEX- The temperature of 02 outlet liquid;Temp probe TI-03 is used to test the temperature of MI-01 outlets liquid;Temp probe TI-04 is used for Test the temperature of R-01 outlets liquid;Temp probe TI-05 is used to test the temperature of HEX-03 outlets liquid;5 temp probes It is connected on temperature indicator.
Embodiment 1
It is prepared by Beta-alanine:With 80% aminopropionitrile of content (technical grade) aqueous solution;30% sodium hydroxide of content is water-soluble Liquid is raw material.
Technological operation step:
1) connection of micro-reactor apparatus:All devices are connected as shown in Figure 1, use Starlam3000 microreactors;
2) debugging of micro-reactor apparatus:Constant temperature circulating machine is opened, 110 DEG C of set temperature is injected by constant flow pump water micro- In consersion unit, micro-reactor apparatus internal duct 10min is cleaned, opening simultaneously counterbalance valve makes system back pressure 5.0MPa, and inspection is set No leakage, gas leak phenomenon are had, whether numerical value is accurate for temperature, pressure monitor equipment, is carried out in next step after all are errorless;
3) flux modification of constant flow pump:Using water as medium calibrated flow, error is no more than setting value by constant flow pump P01, P02 1%;
4) prepare:Aminopropionitrile solution 10g storage tanks are connected to constant flow pump P01,10% sodium hydroxide solution 56.56g storage Tank is connected to constant flow pump P02, and the microreactor inlet temperature of sodium hydrate aqueous solution all the way is 100 DEG C, microreactor outlet temperature 108 DEG C of degree, after equilibration time 5min, reaction temperature rises to 110 DEG C, starts charging reaction;
5) mixed in micro-mixer U, through shell-and-tube reactor, heat exchanger, time 1.5min completes hydrolysis;
6) material that reaction is completed enters receiving tank V-03, and vapor detection, aminopropionitrile conversion ratio are sent in cooling stirring 99.9%;
7) separation is neutralized:By alanine sodium water solution by ion exchange column, neutralization reaction and desalination are carried out, obtains ammonia Base propionic acid aqueous solution;
8) crystallization filters:Alanine aqueous solution is evaporated under reduced pressure and is removed water, white crystal i.e. alanine is obtained by filtration 12.45g product yield:98%;
9) micro-reactor apparatus cleans:Constant temperature circulating machine is closed, micro-reactor apparatus pipeline is rinsed with water by constant flow pump 10min;
Embodiment 2
It is prepared by 3- mercaptopropionic acids:With the 3- sulfydryl propionitrile of content 95%, 20% hydrochloric acid solution is raw material without using solvent.
Technological operation step:
1) microreactor system is attached, and debugs same aforesaid operations;
2) prepare:The 3- sulfydryl propionitrile 5g that content is 95% is placed in holding vessel V-01 and is stored, by pumping P-01 chargings;It will 20% hydrochloric acid solution 10.92g is placed in storage in holding vessel V-02 and is fed by pumping P-02, to the microreactor entrance of hydrochloric acid solution Temperature is 110 DEG C, 114 DEG C of microreactor outlet temperature, and after equilibration time 5min, reaction temperature rises to 115 DEG C, starts to connect Material;
3) mixed in micro-mixer U, through shell-and-tube reactor, heat exchanger, time 1min completes hydrolysis;
4) material that reaction is completed enters receiving tank V-03, and cooling stirring send vapor detection, to 3- sulfydryl propionitrile conversion ratios 99.99%;
5) be concentrated under reduced pressure water outlet, distills out product 3- mercaptopropionic acids 5.2g;
6) micro-reactor apparatus cleans:Constant temperature circulating machine is closed, micro-reactor apparatus pipeline is rinsed with water by constant flow pump 10min。
Embodiment 3
It is prepared by 7 Α-double pyrrolizidine pyridine-acetic acid:With 7 Α of Pilsicainide intermediate-double pyrrolizidine pyridine-acetonitrile, 36% salt Acid solution is raw material.
Technological operation step:
1) microreactor system is attached, and debugs same aforesaid operations;
2) prepare:7 Α of Pilsicainide intermediate-double pyrrolizidine pyridine-acetonitrile 10g that content is 95% is placed in holding vessel Storage in V-01, by pumping P-01 chargings;By 36% hydrochloric acid solution 14.13g be placed in holding vessel V-02 storage by pump P-02 into Material, the microreactor inlet temperature of hydrochloric acid solution all the way are 100 DEG C, 103 DEG C of microreactor outlet temperature, equilibration time 5min Afterwards, reaction temperature rises to 105 DEG C, starts splicing;
3) mixed in micro-mixer U, through shell-and-tube reactor, heat exchanger, time 3min completes hydrolysis;
4) material that reaction is completed enters receiving tank V-03, and vapor detection, 7 Α-double pyrrolizidine pyridine-second are sent in cooling stirring Nitrile conversion ratio 95%;
5) 10~15 DEG C are cooled to, there is solid precipitation, the hydrochloride of 7 Α of product-double pyrrolizidine pyridine-acetic acid is obtained by filtration 12.35g;
6) micro-reactor apparatus cleans:Constant temperature circulating machine is closed, micro-reactor apparatus pipeline is rinsed with water by constant flow pump 10min。
Embodiment 4
It is prepared by 2- amino -2,3- acid dimethyls:With the 2- amino -2,3- nitrile dimethyls of content 95%, 95% it is dense Sulfuric acid is raw material.
Technological operation step:
1) microreactor system is attached, and debugs same aforesaid operations;
2) prepare:2- amino -2,3- nitrile dimethyls 10g that content is 95% is placed in storage in holding vessel V-01, by Pump P-01 chargings;95% concentrated sulfuric acid solution 9.87g is placed in storage in holding vessel V-02 to be fed by pumping P-02, concentrated sulfuric acid solution Microreactor inlet temperature all the way is 100 DEG C, 98 DEG C of microreactor outlet temperature, after equilibration time 5min, in reaction temperature 100 DEG C are risen to, starts splicing;
3) mixed in micro-mixer U, through shell-and-tube reactor, heat exchanger, time 0.5min completes hydrolysis;
4) material that reaction is completed enters receiving tank V-03, and vapor detection, 2- amino -2,3- dimethyl are sent in cooling stirring Butyronitrile conversion ratio 99%;
5) near 20~30 DEG C of temperature with ammonium hydroxide tune pH value extremely in alkalescent, with Toluene extractive reaction liquid, concentrate toluene, Obtain product 2- amino -2,3- amide dimethyl butyrates 11.48g.
6) micro-reactor apparatus cleans:Constant temperature circulating machine is closed, micro-reactor apparatus pipeline is rinsed with water by constant flow pump 10min。
Embodiment 5
The preparation of phenylacetic acid:Using 98% benzene acetonitrile of content, 10% sodium hydroxide as raw material.
Technological operation step:
1) microreactor system is attached, and debugs same aforesaid operations;
2) prepare:The benzene acetonitrile 10g that mass content is 98% is placed in holding vessel V-01 and is stored, by pumping P-01 chargings; 10.0% sodium hydroxide solution 86mmol is placed in storage in holding vessel V-02 to be fed by pumping P-02, sodium hydrate aqueous solution one The microreactor inlet temperature on road is 100 DEG C, 102 DEG C of microreactor outlet temperature, after equilibration time 5min, in reaction temperature 105 DEG C are risen to, starts splicing;
3) mixed in micro-mixer U, through shell-and-tube reactor, heat exchanger, time 1min completes hydrolysis;
4) material that reaction is completed enters receiving tank V-03, and vapor detection, benzene acetonitrile conversion ratio are sent in cooling stirring 98.9%;
5) there is product precipitation after being adjusted to PH=1~2 with hydrochloric acid after stirring 30min, centrifuge, obtain product 11.27g, product is received Rate 97%;
6) micro-reactor apparatus cleans:Constant temperature circulating machine is closed, micro-reactor apparatus pipeline is rinsed with water by constant flow pump 10min;
Embodiment 6
Preparation to sodium chloroacetate:Using 98% p-chlorobenzyl cyanide of content, 10% sodium hydroxide solution as raw material.
Technological operation step:
1) microreactor system is attached, and debugs same aforesaid operations;
2) prepare:The p-chlorobenzyl cyanide 8g that mass content is 98% is placed in holding vessel V-01 and stores, by pump P-01 into Material;10.0% sodium hydroxide solution 21.41g is placed in storage in holding vessel V-02, and, by pumping P-02 chargings, sodium hydroxide is water-soluble The microreactor inlet temperature of liquid all the way is 110 DEG C, 112 DEG C of microreactor outlet temperature, after equilibration time 5min, reaction temperature Degree rises to 116 DEG C, starts splicing;
3) mixed in micro-mixer U, through shell-and-tube reactor, heat exchanger, time 3min completes hydrolysis;
4) material that reaction is completed enters receiving tank V-03, and vapor detection, p-chlorobenzyl cyanide conversion ratio are sent in cooling stirring 99.99%;
5) PH=1~2 are adjusted to hydrochloric acid, have product precipitation after stirring 30min, centrifuged, obtain product 8.91g, product yield 99%;
6) micro-reactor apparatus cleans:Constant temperature circulating machine is closed, micro-reactor apparatus pipeline is rinsed with water by constant flow pump 10min。
Embodiment 7
It is prepared by beta-phenoxy propionic acid:With the 3- phenoxypropionitriles of content 98%, 36% concentrated hydrochloric acid, for raw material, glacial acetic acid Make solvent.
Technological operation step:
1) microreactor system is attached, and debugs same aforesaid operations;
2) prepare:The 3- phenoxypropionitriles 10g that content is 98% is dissolved in 20mL glacial acetic acid, is placed in holding vessel V-01 Interior storage, by pumping P-01 chargings;By 36% concentrated hydrochloric acid solution 7.15g, it is placed in storage in holding vessel V-02 and is fed by pumping P-02, The microreactor inlet temperature of concentrated hydrochloric acid solution all the way is 100 DEG C, 98 DEG C of microreactor outlet temperature, after equilibration time 5min, Reaction temperature rises to 100 DEG C, starts splicing;
3) mixed in micro-mixer U, through shell-and-tube reactor, heat exchanger, time 2min completes hydrolysis;
4) material that reaction is completed enters receiving tank V-03, and vapor detection, 3- phenoxypropionitrile conversion ratios are sent in cooling stirring 98%;
5) near 20~30 DEG C of temperature, are diluted with cold water, obtain white flock beta-phenoxy propionic acid crude product 10.73g.
6) micro-reactor apparatus cleans:Constant temperature circulating machine is closed, micro-reactor apparatus pipeline is rinsed with water by constant flow pump 10min;

Claims (10)

1. a kind of method that micro passage reaction carries out the reaction of cyano class compound hydrolysis, it is characterised in that:Contain cyanogen in molecule The compound of base group (- C ≡ N) in a solvent, adds in alkalescence or acidic materials, using micro channel reactor system in 0-150 DEG C, under the conditions of 0.1-10Mpa, the reaction that is hydrolyzed.
2. according to the method described in claim 1, the compound containing cyano group (- C ≡ N) is aliphatic in the molecule Compound.
3. according to the method described in claim 1, it is characterized in that:Contain cyano group (- C ≡ N) compound in the molecule Structure at least contain that there are one the cyano group of reaction can be hydrolyzed.
4. according to the method described in claim 1, it is characterized in that:The alkaline matter is sodium hydroxide, potassium hydroxide, carbonic acid One in sodium, potassium carbonate at least plants.
5. according to the method described in claim 1, it is characterized in that:The acidic materials are sulfuric acid, hydrochloric acid, in phosphoric acid at least It is a kind of.
6. according to the method described in claim 1, it is characterized in that:The solvent is water, alcohols or glacial acetic acid.
7. according to the method described in claim 1, it is characterized in that:Micro- reaction system includes the raw material being sequentially communicated storage Tank, feed pump, heat exchanger, micro-mixer, shell-and-tube reactor, heat exchanger.
8. according to the method described in claim 1, it is characterized in that:By micro passage reaction by counterbalance valve back pressure, microchannel plate It answers and reaches pressure in device system, raw material is fed through feed pump, is mixed in micro-mixer, through shell-and-tube reactor, heat exchanger one Determine to complete hydrolysis class reaction at temperature.
9. according to the method described in claim 1, it is characterized in that:In molecule containing cyano group (- C ≡ N) compound with Alkalescence or the molar ratio of acidic materials are 1:1-6.
10. according to the method described in claim 1, it is characterized in that:The reaction of the hydrolysis is 0.1s-60min.
CN201711463244.3A 2017-12-28 2017-12-28 Method for carrying out cyano hydrolysis reaction by using microchannel reactor Active CN108084192B (en)

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Application Number Priority Date Filing Date Title
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US12030906B2 (en) 2017-05-01 2024-07-09 Gilead Sciences, Inc. Crystalline forms of (s)-2-ethylbutyl 2-(((s)-(((2r,3s,4r,5r)-5-(4-aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy) (phenoxy) phosphoryl)amino)propanoate
CN109796384A (en) * 2019-04-02 2019-05-24 禄丰天宝磷化工有限公司 Method for continuously and rapidly preparing 2-hydroxy-4-methylthiobutyrate
CN115298181A (en) * 2020-03-12 2022-11-04 吉利德科学公司 Method for preparing 1'-cyano nucleoside
US12012431B2 (en) 2020-03-12 2024-06-18 Gilead Sciences, Inc. Methods of preparing 1′-cyano nucleosides
CN111333525A (en) * 2020-04-15 2020-06-26 大连韦德生化科技有限公司 A kind of continuous production process of β-alanine
CN111704538A (en) * 2020-06-15 2020-09-25 杭州迈科瑞科技有限公司 Method for preparing p-hydroxyphenylacetic acid by using microreactor
US12297226B2 (en) 2020-08-27 2025-05-13 Gilead Sciences, Inc. Compounds and methods for treatment of viral infections
CN112552245A (en) * 2020-12-29 2021-03-26 苏州正济药业有限公司 Synthesis method of Favipiravir
CN112552245B (en) * 2020-12-29 2022-08-02 苏州正济药业有限公司 Synthesis method of Favipiravir
US12180217B2 (en) 2022-03-02 2024-12-31 Gilead Sciences, Inc. Compounds and methods for treatment of viral infections
CN116514818A (en) * 2023-04-25 2023-08-01 诚弘制药(威海)有限责任公司 Preparation method of piracy carnitinib intermediate

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